Studies have been performed on tissues obtained from human hearts. It has been learned that a resting cardiac cell has a transmembrane voltage difference of about 90 mV. The inside of the cell is negative relative to the extracellular fluid and, upon cell stimulation, an action potential ensues. The action potential consists of five phases. Phase 0 is rapid depolarization, phase 1 is an early repolarization, phase 2 is the plateau phase, phase 3 is a rapid repolarization to the diastolic transmembrane voltage, and phase 4 is the diastolic period. The time-voltage course of the action potential varies among different cardiac cell types.
The electrical charge of the outer membrane of individual heart muscle cells is known as the membrane potential. During each heart beat, the membrane potential discharges (depolarizes) and then slowly recharges (repolarizes). The waveform of this periodic depolarization and repolarization is called the "transmembrane action potential." Mechanistically, the action potential is produced by a well-organized array of ionic currents across the cell membrane.
The transmembrane action potential has typically been recorded by means of microelectrodes, which are extremely fine glass capillaries that can be impaled into a single heart muscle cell. Because of the fragility of the glass capillary and the small dimensions of the heart cell, such recordings can be obtained only in small isolated tissue preparations, which are excised from animal hearts and are pinned down in a chamber with artificial solution. It is impossible to use the microelectrode technique in the intact beating heart, such as in patients.
Most of our knowledge about the electrophysiologic properties of the heart is based on the use of microelectrodes. However, because the microelectrode cannot be used in the human heart, there has been a lack of data relating to the elementary processes in the in vivo human heart, which may be different from the processes of the in vitro heart, particularly in disease.
At the turn of the century, it had already been recognized that a potential similar in shape to the later-discovered transmembrane potential could be recorded if one electrode was brought into contact with an injured spot of the heart and the other electrode with an intact spot. Those signals became known as "injury potential" or "monophasic action potentials" (MAPs) because of the waveform shape. When it was found that the injury could be produced by suction, so-called suction electrodes were developed. Thus, to examine the time course of local electrical activity under experimental conditions in which microelectrode recordings are difficult or impossible to make, such as in the vigorous beating in-situ heart, investigators have often used suction electrodes. The signal obtained with suction electrodes is monophasic and, although of smaller amplitude, accurately reflects the onset of depolarization and the entire repolarization phase of transmembrane action potentials recorded from cells in the same vicinity. Suction electrodes have also been used in human subjects, but the potential for subendocardial damage and S-T segment elevation has limited its clinical use to short recording periods of two minutes or less. Because the shape and duration of the action potentials vary from site to site in the heart, longer recording time from a single endocardial site is needed to evaluate long-term MAP changes, such as heart rate effects over several basic cycle lengths or in response to pharmacologic interventions. These longer recording times have not been achievable, however, with suction electrodes, because of the resulting damage to the tissue. Primarily for this reason, the suction electrode technique has never gained wide clinical acceptance. Therefore, the gap between microelectrode studies in excised animal tissue and what is possible in the intact human heart has remained large. There still was no safe and reliable method to obtain such signals in the human heart itself, which could provide the most valuable information,without damage to the myocardium.
Applicants herein have recognized that local heart muscle injury is not a prerequisite for the generation of MAPs, and that application of slight pressure with the tip against the inner wall of the heart would result in monophasic elevations of the signal if the filter settings were left wide open, i.e., from 0 to 5,000 Hz. Based on a theoretical evaluation of the signal modality and the factors that are responsible for its creation, applicants have found that these signals can be recorded reliably (i.e., without distortion) by using direct current (DC) coupled to amplification.
In the past, no provision has been made for measuring the electrophysiological activity of a heart in the immediate vicinity in which the heart is activated by a pacing catheter. Moreover, if it is desired to pace the heart at the same time as measuring MAPs in the heart, two entrance sites to the patient must be created and two catheters must be utilized, which is highly undesirable.
Because of the complexity of electrical cardiac activity, when a pacing electrode is inserted into the heart, and it is desired to measure the resulting action potentials of the heart, it would be of extreme usefulness to be able to measure such potentials in the vicinity of the activation, rather than at a more remote location.
Another problem to overcome is the slow DC drift caused by electrode polarization in conventional electrical material used in the recording of intracardiac electrical signals, such as silver or platinum. These materials are polarizable and cause offset and drift-which is not a problem in conventional intracardiac recordings, because those signals are AC coupled, which eliminates offset and drift. The MAPs, however, are to be recorded in DC fashion, and therefore are susceptible to electrode polarization. Applicants found that the use of a silver-silver chloride electrode material yields surprisingly good results in terms of both long-term stability of the signal and extremely low noise levels.
Another important discovery herein has been that the tip electrode of the catheter should be held against the inner surface of the heart with slight and relatively constant pressure. In order to accomplish this in a vigorously beating heart, a spring-steel stylet is inserted into a lumen of the catheter of the present invention to act as an elastic coil, keeping the tip electrode in stable contact pressure with the endocardium throughout the cardiac cycle. This leads to major improvements in signal stability.
Thus, a main feature of the catheter of the present invention is to bring into close and steady contact with the inner surface of the myocardial wall a nonpolarizable electrode which both produces and records MAPs. To achieve this property, the electrodes are formed from nonpolarizable material such as silver-silver chloride, and the tip electrode should be maintained at a relatively constant pressure against the myocardial wall, preferably with some type of spring loading. The endocardial embodiment of the catheter of the present invention contains a spring-steel guide wire which provides this high degree of elasticity or resilience which allows the catheter tip to follow the myocardial wall throughout the heartbeat without losing its contacting force and without being dislodged. The inner surface of the heart is lined with crevices and ridges (called the trabeculae carneae) and are helpful in keeping the spring-loaded catheter tip in its desired location. The contact pressure exerted by the tip electrode against the endocardial wall is strong enough to produce the amount of local myocardial depolarization required to produce the MAP. The contact pressure is, on the other hand, soft and gentle enough to avoid damaging the endocardium or the myocardium or cause other complications. In particular, no cardiac arrhythmias are observed during the application of the catheter. Usually a single extra beat occurs during the initial contact the catheter tip against the wall, when it is observed. This is a result of the stable continuous contact of the tip electrode against the heart muscle, which is provided by the spring inside the catheter shaft.
It is the tip electrode which is responsible for the generation and the recording of the MAP itself. A reference electrode, required to close the electrical circuit, is located approximately 3 to 5 mm from the tip electrode in the catheter shaft and is embedded in the wall so that it is flush with or slightly recessed in the catheter shaft, and makes contact only with the surrounding blood and not with the heart wall itself.
This reference electrode is brought into close proximity with the tip electrode, since the heart as a whole is a forceful electrical potential generator and these potentials are present everywhere in the cardiac cavities. If the reference electrode were in a remote location, then the amplifier circuit would pick up the QRS complex.
Another design feature important for the purpose of the MAP catheter is to ensure a relatively perpendicular position of the electrode tip with the endocardial wall. Again, the spring electrode is useful in this respect. Conventional catheters are usually brought into contact with the heart wall in a substantially tangential manner. Such conventional catheters are designed simply to record intercardiac electrograms, not MAPs. For the monophasic action potential catheter, direct contact of between the tip electrode and the endocardium is made. This also keeps the reference electrode, which is located along the catheter shaft, away from the heart muscle.
To facilitate the maneuverability of the catheter during a procedure in the human heart, the distal end of the catheter should be relatively flexible during the time of insertion, and the spring-loading feature preferably comes into action only after a stable position of the catheter tip has been obtained. Thus, in a preferred embodiment the catheter is constructed in such a way that the spring wire situated in the lumen of the catheter is retractable. During catheter insertion, the spring wire or stylet is withdrawn from its distal position by approximately 5 cm, making the tip relatively soft. Once the catheter is positioned, the spring wire is again advanced all the way into the catheter in order to stiffen it and to give it the elastic properties that are important for the described properties.
Important applications of the present invention are in the areas of directly studying the effects of drugs (for example, antiarrhythmia agents such as procainamide and quinidine) on the heart in real time; studying myocardial ischemia, and in particular, precisely locating areas of myocardial ischemia by studying localized MAPs; and diagnosing the nature and locality of arrhythmias originating from after-depolarizations. These after-depolarizations have hitherto been detected only in isolated animal tissue preparations where microelectrodes can be applied. The MAP catheter is a tool that can allow the clinical investigator to detect such abnormal potentials in the human heart and thereby significantly broaden our ability to diagnose this group of arrhythmias.
A field of study related to the measurement of MAPs is the actual pacing of in vivo hearts to generate such MAPs. A problem with current devices for pacing the heart lies in the fact the pacing threshold is relatively high, such that battery life for portable pacemakers is short.